【作者】 李海花；

【导师】 田仕凯；

【作者基本信息】 中国科学技术大学 ， 有机化学， 2010， 博士

【摘要】 醇是一类价廉易得的有机化合物,可以方便而有效地转化为相应的卤代烃、磺酸酯、羧酸酯和磷酸酯等衍生物。这些醇衍生物在酸性条件下能够与多种亲核试剂发生取代反应,从而间接地实现醇羟基的取代,但不可避免地产生酸性副产物,导致更多的副反应。相对而言,直接取代醇羟基不仅节省一步反应,而且生成的副产物是水,具有原子经济性,并减少副产物。然而醇羟基不容易离去,直接取代的反应类型很少。我们利用酸性副产物或者外加酸性催化剂实现了醇与多种亲核试剂的直接取代反应,有效地拓展了醇的合成应用范围。发展了副产物催化的醇、酰氯和六甲基二硅胺烷三组分反应,合成多取代酰胺。酰氯和六甲基二硅胺烷反应的副产物是三甲基氯硅烷,被醇分解而产生的氯化氢能够将醇及其衍生物转化为相应的碳正离子,然后与原位形成的N-硅基酰胺反应。苄型、烯丙型醇是合适的反应底物,而氯甲酸酯、磺酰氯可以代替酰氯,合成相应的氨基甲酸酯、磺酰胺。发展了副产物催化的醇和亚磺酰氯的反应,合成了一系列苄型、烯丙型砜。醇和亚磺酰氯反应生成亚磺酸酯,然后在副产物氯化氢的催化下生成碳正离子和亚磺酸,两者结合便生成砜。另外,醇在氯化氢的作用下也可以生成碳正离子和水,后者分解亚磺酰氯而产生亚磺酸。发展了三氟甲磺酸酐/三氯化铁/硝酸银三组分试剂催化的苄型醇、端炔和芳烃三组分反应,通过调控催化剂组成和反应温度,以很高的立体选择性合成Z-或者E-三取代烯烃。苄型醇在酸性催化剂作用下转化为苄基正离子,进攻端炔而形成烯基正离子,再与芳烃反应,生成三取代烯烃。发展了三氟甲磺酸酐催化的苄型醇和烯烃的反应,高立体选择性的合成多取代烯烃和2,3-二氢茚类化合物。一般而言,苄型醇和端烯反应生成三取代烯烃；而1,2-二取代、三取代烯烃的反应生成2,3-二氢茚类化合物。利用相应的醇来原位生成烯烃,也能够以同样高的立体选择性合成多取代烯烃和2,3-二氢茚类化合物。发展了硫酸催化的磺酰胺和烯烃(或者醇)的反应,高选择性地合成多取代烯烃和2,3-二氢茚类化合物。在酸性条件下磺酰胺的sp3碳-氮键发生断裂,产生碳正离子,然后与烯烃进行烯化或者[3+2]环化反应。更多还原

【Abstract】 Readily available and inexpensive alcohols can be easily transformed into the corresponding halides, sulfonates, carboxylates, and phosphonates, which are able to react with a wide variety of nucleophiles under acid conditions. However, such indirect substitution of the hydroxyl groups in alcohols inevitably generates acidic byproducts that lead to more side reactions. In contrast, direct substitution of the hydroxyl groups in alcohols not only saves one step of synthetic manipulation, but also suppresses side reactions and exhibits atom-economy by generating byproduct water. Nevertheless, limited procedures have been disclosed for direct substitution of the hydroxy groups in alcohols owing to their poor leaving ability. Herein we disclose the direct substitution of the hydroxy groups in alcohols with serveral nucleophiles in the presence of acidic byproducts or external acidic catalysts. These studies significantly extend the synthetic applications of alcohols.The three-component reaction of alcohols, acyl chlorides, and hexamethyldisilazane has been developed through byproduct catalysis for the synthesis of polysubstituted amides. Trimethylchlorosilane is generated as a byproduct from acyl chlorides and hexamethyldisilazane, and is consequently decomposed by alcohols. The resulting HCl promotes the decomposition of alcohols and/or their derivatives to generate carbocations, which couple with N-silylamides generated in situ to afford amides. Benzylic and allylic alcohols serve as suitable substrates, and the replacement of acyl chlorides with chloroformates and sulfonyl chlorides results in the formation of N-alkyl carbamates and sulfonamides, respectively.The reaction of alcohols with sulfinyl chlorides has been developed through byproduct catalysis for the synthesis of benzylic and allylic sulfones. Initial reaction of alcohols with sulfinyl chlorides yield sulfinate esters that are ready to decompose in the presence of byproduct HCl, and the resulting carbocations and sulfinic’acids are coupled to afford sulfones. Alternatively, HCl promotes the decomposition of alcohols to generate carbocations and water, and the latter react with sulfinyl chlorides to afford sulfinic acids.The three-component reaction of terminal alkynes, benzylic alcohols, and simple arenes has been developed in the presence of a catalytic amount of triflic anhydride/ferric trichloride/silver nitrate. An array of both Z-and E-isomers of trisubstituted alkenes have been obtained with excellent stereoselectivity simply by switching the acidic catalyst system and reaction temperature. Regioselective attack of terminal alkynes by carbocations, generated in situ from benzylic alcohols in the prescence of acidic species, results in the formation of vinyl cations, which undergo an electiophilic aromatic substitution reaction with arenes to afford trisubstituted alkenes.The reaction of benzylic alcohols with alkenes has been developed in the presence of triflic anhydride for the synthesis of polysubstituted alkenes and indane derivatives with high stereoselectivity. In general, benzylic alcohols react with terminal alkenes to afford trisubstituted alkenes, and the reaction with 1,2-disubstituted and trisubstituted alkenes affords indane derivatives. In addition, the employment of alkenes generated in situ from the corresponding alcohols under the acidic reaction conditions also affords polysubstituted alkenes and indane derivatives with high stereoselectivity.The reaction of sulfonamides with alkenes (or the corresponding alcohols) has been developed in the presence of sulfuric acid for the synthesis of polysubstituted alkenes and indane derivatives with high stereoselectivity. The sp3 carbon-nitrogen bonds of sulfonamides are cleaved under acidic conditions to generate carbocations, which undergo olefination reaction or [3+2] annulation reaction with alkenes.更多还原